The purpose of this project is to advance our understanding of the role that disturbances of dopamine (DA) and prefrontal cortex (PFC) play in producing the cognitive deficits observed in schizophrenia. The basic science projects in this Center will study the anatomy and physiology of intrinsic prefrontal cortical circuitry, and its modulation by DA and other monoamines. In this project, we will address the role that these systems play in human behavior, and in producing cognitive deficits observed in schizophrenia. The studies are motivated by a series of parallel distributed processing (PDP) models that address the computational function of PFC, its regulation by DA neuromodulation, and the disturbance of this system in schizophrenia. These models suggest that behavioral inhibition and memory - two functions that have often been treated as distinct, and dissociable functions of PFC - may simply be two features of a single underlying process subserved by PFC: the representation and maintenance of information needed to select task appropriate responses (context information). This hypothesis makes specific predictions about eh pattern of cognitive deficits that should be observed in tasks that assess subjects' ability to represent context information, maintain this information over temporal delays, and use it to inhibit competing responses. Furthermore, it makes predictions about how the pattern of deficits should evolve over the course of illness. The primary goal of this project will be to test these predictions in behavioral studies (cognitive and eye-movement tasks, and neuropsychological assessments), and to continue to develop the computational models upon which they are based, constrained by new behavioral and biological data.